1. Field of the Invention
The invention relates to a process for the production of endotropine by the reduction of tropanone with hydrogen catalytically activated by Raney nickel or Raney copper catalyst. Tropine is also known as 3.alpha.-tropanol, 3.alpha.-hydroxytropane, 1.alpha.H, 5.alpha.H-tropan-3.alpha.-ol, and 8-methyl-8-azabicyclo-[3,2,1]-nonan-3.alpha.-ol (CAS [120-29-6]).
2. Description of the Prior Art
Endotropine is an important substance for the production of nortropine by oxidative methylation, which is in turn used for the production of important azoniaspironortropanol esters, which are used as pharmaceuticals, particularly spasmolytics (cf. German patent 1 194 42).
U.S. Pat. No. 2,366,760 describes the preparation of tropine from tropanone by catalytic reduction with hydrogen activated by a Raney nickel catalyst, without giving the yield. The reaction is performed under pressure and in an organic solvent, preferably ethanol, giving a quantitative yield. This procedure involves high apparatus expenditure with pressure vessels or autoclaves. By the use of organic solvents in conjunction with Raney nickel catalysts there is a high fire or explosion risk when working up the reaction batch. Corresponding accidents are well known from practical experience.
U.S. Pat. No. 2,746,976 describes the preparation of tropine, using an autoclave as the reaction vessel and an organic solvent, at an operating pressure of 60 atmospheres overpressure. The aforementioned disadvantages once again arise. Chemical Abstract 99 (15), 122, 721 a describes a catalytic hydrogenation of tropanone in the presence of a rhodium-phosphine complex.
Processes in which endotropine is produced by the hydrogenation of tropanone in the presence of a Raney nickel catalyst are shown in (Chemical Abstracts 97 (23), 198, 428q, Chemical Abstracts 93 (13), 132 665a and Chemical Abstracts 83 (23), 193 5611). In the first-mentioned literature reference, a yield of 92% is given. Thus, the hitherto known processes only make it possible to produce tropine in the presence of organic solvents and when using a high pressure.
It has now been surprisingly found that it is possible to reduce tropanone selectively and with good yields without using a high pressure and without using organic solvents so as to give tropine when an aqueous mixture of tropanone is reduced by hydrogen when subjected to turbulent action at atmospheric pressure and ambient temperatures at 1000 to 1500 r.p.m. It could not be foreseen on the basis of the hitherto known processes that this reaction would take place smoothly and also stereoselectively supplies the desired endotropine compound.